future opportunities for food tech product innovation from a research perspective

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  • Diet has strong effects on aging and diseases such as cancer

    Over-eatingCalorie Restriction (CR)

    How does diet regulate organ regeneration and cancer?

  • Organism) Lifespan)increase)with)caloric)restric4on)(CR))Yeast& 3(fold&Worms& 2(3&fold&Flies& 2(fold&Mice& 30(50%&Monkeys& 10%&or&no&eect&Humans) Not)studied)

    Fontana L et al. Science. 2010 Apr 16;328(5976):321-6 Mattison, J. A. et al. Nature 489, 318321 (2012) Coleman RJ et al. Nat Commun. 2014 Apr 1;5:3557

    Extending life span with caloric restriction - from yeast to humans

  • Lgr5+ stem cells at the base of crypts maintain the intestinal epithelium

    Clevers,Nature2007;Lewis,NatureReviewsGene2cs2006

    Lgr5+

    Lgr5Lgr5

    Lgr5Lgr5

    GFPhi

    GFPlow

    Lgr5+ stem cell

    Paneth cell niche

  • T Sato et al. Nature 000, 1-4 (2009) doi:10.1038/nature07935

    Single Lgr5+ cells generate cryptvillus structures.

    Sato et al 2009 Yilmaz et al 2012

    Engineering mini-intestines in culture

    Test effects of dietary components in 3-D miniature organs

  • cADPR

    Calorie restriction

    mTORC1

    differentiation

    self-renewal

    Effect of a low calorie state on stem cells

    Can CR or its mimetics enhance intestinal regeneration in patients?

  • Enema of cADPR heals intestinal injury

  • Smoking

    Overweight and obesity

    Lack of exercise

    Diet

    Occupation

    Viruses

    Family history

    Alcohol

    UV and ionizing radiation

    Prescription Drugs

    Reproductive factors

    Pollution

    adapted from Colditz et al., Science Translation Medicine, 2012

    Smoking

    Overweight and obesity

    Obesity is a diet-modifiable cause of cancer

  • HFD boosts stem cell function

    Control

    HFD

    **

    *

    *

    * *

    *

    0

    0.2

    0.4

    0.6

    0.8

    Control' HFD'

    Org

    anoi

    d pe

    r cry

    pt

    '

    *

  • Palmitic acid is an abundant component of the HFD

    Palmitic Acid

  • PAVehicle

    organoids from crypts

    Vehicle PA

    2

    1

    0

    3

    4 *%

    GFP

    hi p

    ositi

    ve s

    tem

    cel

    ls

    Org

    anoi

    d pe

    r ste

    m c

    ell

    Vehicle PA

    Vehicle

    PA

    Side

    Sca

    tter A

    rea

    EGFP

    1.5 0.3%

    3.3 0.7%**0

    0.06

    0.04

    0.02

    0.10

    0.08

    **0.12

    Ex vivo exposure of mini-intestines to Palmitic Acid boosts stem cell numbers and function

    Similar results observed with oleic acid and other lipids

  • If stem cell activity increases, HFD should raise tumor incidence

    mutation

  • If stem cell activity increases, HFD should raise tumor incidence

    Inci

    denc

    e

    0.8

    0.6

    0.4

    0.2

    0.7

    0.5

    0.3

    0.1

    Number of intestinal carcinoma per mouse

    Aged Aged+HFD

  • Potential contributor to obesity-induced increase in cancer incidence?